The ultimate objective of this project is to obtain a physical description of the molecular processes underlying ion movements during excitation of a nerve membrane. The short-term objectives are to obtain information on the fundamental properties of K and Na conduction in the model squid nerve preparation. The questions to be addressed are the following: 1) Are the elementary processes at equilibrium? 2) Are their kinetics linear or nonlinear? 3) Are their kinetics dependent on ion species or on concentration? 4) How many conducting states are involved? The measurement techniques used in these studies are centered around an internal axial-electrode voltage-clamp system, which has been improved significantly with respect to background noise. Rapid transfer function determinations are made by using synchronized, Fourier-synthesized pseudorandom signals as perturbations superposed on step clamps of membrane potential in combination with fast Fourier transform computations. The complex admittance is obtained in the frequency range 12.5-5000 Hz, where the ion conduction properties dominate the admittance. Linear analysis is carried out by curve fitting the complex admittance data using linear models. Power spectra of spontaneous current fluctuations are also obtained under the same conditions as the admittance determinations and in the same axons. Model fits of power spectra yield kinetic parameters which are compared and used with the admittance data to provide the information necessary to resolve the above questions. In the second part of the project, the origin, statistical properties and interactions of noise generating processes in isolated components of the squid axon will be studied. These measurements will provide information that will enable more effective use of noise data in discriminating between microscopic models of the elementary ion-current processes. Glass micropipets will be used to isolate and record the conduction properties of axoplasm, portions of the subaxolemmal filamentous network, and axolemma channels with and without the Schwann cell layer.